Hypothetical case scenario
27-year old female presents to the office with a complaint of irregular periods. Menarche was at age 15, and periods occur about 1-2 times a year. Breast development began at age 9, followed shortly by axillary & pubic hair. Growth spurt was at age 13. She’s been trying to get pregnant for the last one year now, and has never been seen before for her irregular periods.
On physical exam, she is overweight with a Body Mass Index (BMI) of 26, exhibits mild facial hair (hirsutism), and shows brown thickening of the skin behind her neck (Acanthosis Nigracans).
This patient exhibits classic signs and symptoms of someone with Polycystic Ovarian Syndrome (PCOS), a common disorder which affects up to 10% of women. It is one of the most common causes of dysfunctional uterine bleeding, with a complaint of irregular periods being the most common presenting complaint to the doctor. The PCOS diagnostic criteria were developed by the National Institute of Health (NIH) in 1990, and include the following:
1. Hyperandrogenism: These women tend to have more androgen (the classic male sex hormones) levels floating around in their system, causing hirsutism, acne, male pattern hair loss (alopecia), and elevated blood testostosterone levels.
2. Chronic Anovulation: These women tend to ovulate less, and therefore exhibit more difficulty with their periods. They may lack periods all together (Amenorrhea), have cycles that last greater than 35 days (Oligomenorrhea), have unpredictable periods (Dysfunctional Uterine Bleeding), or report of infertility with difficulty reaching pregnancy.
3. All secondary causes of the above must be ruled out: Pregnancy, Thyroid Disease, Eating Disorders, Exercise Related Amenorrhea, Hypothalamic-Pituitary Disorder, Premature Ovarian Failure, Pituitary Adenoma, Congenital Adrenal Hyperplasia, and Cushings Disease.
The name is a misnomer, since having cysts on the ovaries is not a criterion of this disorder. Up to 20% of healthy women may exhibit cysts on the ovaries, and do not have PCOS. Obtaining a pelvic ultrasound to search for ovarian cysts is not diagnostic, and should not be ordered. The pathophysiology includes two pathways.
First, there is a specific chemical released from the hypothalamus in the brain, called Gonadotropin Releasing Hormone (GnRH). When the hypothalamus releases GnRH in a high pulse frequency, as it does in PCOS, it signals to the pituitary gland to preferentially release another chemical called “Lutenizing Hormone,” or LH. This LH stimulates the ovarian cells to produce more androgens, thereby causing PCOS.
The second important pathway of this syndrome is caused by insulin resistance. Insulin resistance occurs in women with a predisposition to diabetes or pre-diabetes, and they often have a family history of this. Insulin is released by your body in response to glucose when you consume sugar. Certain cells have a “doorway” that require insulin to open it in order to allow glucose to enter its cells and become metabolized. When this doorway is malfunctioning, your body continues to release more and more insulin in order to open these malfunctioning doorways. This rise in insulin levels attack your ovaries and directly stimulates them to increase androgen production, thus causing PCOS.
The reason PCOS is important to learn about is not only because of its high incidence, but also its potential complications if left undiagnosed or untreated. Here are some of the more important complications in those with PCOS:
* Decreased Fertility: Although, with good treatment, most women are able to ovulate and become pregnant.
* Endometrial hyperplasia: There is a higher endometrial cancer risk if non-menstruating women do not shed their endometrium, with a three times higher risk of cancer in women who have a period less than four times a year.
* Obesity: 30-40% of PCOS women are also obese.
* Dyslipidemia: Many PCOS women show high triglycerides and LDL levels (your “bad” cholesterols), and low HDL (your “good “cholesterol).
* Insulin Resistance: There is a ten times higher risk of developing Type II Diabetes in PCOS patients. Thirty to forty percent have impaired glucose tolerance. Ten percent have Type II Diabetes by age 40.
* Hyperandrogenism: Many fight a long battle with excess body and facial hair, adult acne, and even male pattern hair loss. Cosmetically, this is a great cause of concern and frustration for many of these women.
* Coronary Artery Disease (CAD): There is also an increased coronary artery calcification in PCOS women. Yet an increase in morbidity or mortality from CAD not yet established.
* Pregnancy Risks: There is a higher rate of reported gestational diabetes, hypertension-related disorders in pregnancy, multiple births, and a 30-50% risk of first trimester miscarriage in those with PCOS.
* Hypertension: Many with obesity also show an increase in blood pressure levels, and require treatment.
* Sleep Apnea: Those with an obesity co-morbidity may also suffer from sleep apnea, and require screening.
There are several treatment options for those with PCOS. The most studied oral medication is metformin, which is a medication given to those with diabetes in order to decrease insulin resistance. It works on the liver to decrease production of glucose, which in turn decreases insulin levels. And if there is less insulin, there is less androgen production by the ovaries. When combined with exercise, it can facilitate weight loss. It also increases fertility, as 40-90% taking metformin report more regular periods and ovulation. It may also help prevent the onset of diabetes in those with PCOS.
Side effects occur in 30%, and include diarrhea and bloating, yet this resolves with time and is minimized if the medication is taken with meals. The extended release formulation of metformin may also help minimize side effects. There is a decrease in the rate of miscarriage to 8.8% compared to 41.9% on placebo, and a decrease in gestational diabetes if conceive while on metformin. Metformin is normally continued during the first trimester of pregnancy, and then stopped when reaching second trimester.
Oral contraceptive pills are also used to treat PCOS women with irregular periods. Several different brands offer a progesterone component that acts as a weak anti-testosterone component, which may add a greater benefit to those with PCOS and elevated androgen levels. This may be of benefit in those with excess hair, male pattern hair loss, or acne. If not considering pregnancy, oral contraceptives will allow the endometrium to shed in order to decrease the risk of hyperplasia and cancer.
Mainstay of treatment, however, is weight loss. With a 5% or greater weight loss, 82% have improved menses over a six to seven month period of time. Like in diabetics, a lower carbohydrate diet is recommended in order to increase insulin sensitivity. Weight loss decreases insulin resistance and improves hirsutism. And with a 5% weight loss, 40% have reported a pregnancy outcome.
In those who desire pregnancy, there are good treatment options available. Clomiphene is the mainstay, and induces ovulation in 75%, and 50% of those who ovulate on Clomiphene will conceive. Most pregnancies occur within the first six ovulatory cycles while on Clomiphene.
Patients with PCOS should consult their physician regarding their individual treatment options.
Jill of All Trades is a family physician who blogs at her self-titled site, Jill of All Trades, MD.
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